Statins may not have as large a protective effect against venous thromboembolism as is believed, according to a meta-analysis of randomized trials.

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Statins may not have as large a protective effect on venous thromboembolism (VTE) disease as is believed.

Note that researchers also did not find any benefits when they controlled for statin type.

Statins may not have as large a protective effect against venous thromboembolism (VTE) as is believed, according to a meta-analysis of randomized trials.

In 22 trials comparing statin use to no statin use, there was no statistically significant reduction in venous thromboembolic events for statin takers (0.9% versus 1%, odds ratio 0.89, 95% CI 0.72 to 1.01, P=0.08), reported Kazem Rahimi, MD, of the University of Oxford in England, and colleagues.

In seven trials comparing higher statin doses with standard therapy, there also was no reduction in VTE events (1% versus 1%, OR 0.98, 95% CI 0.80 to 1.20, P=0.87), according to the study published in the September issue of PLoS Medicine.

When researchers looked individually at deep vein thrombosis or pulmonary embolism in the studies comparing statin use to controls, they found no benefit for statin use (OR 0.85, 95% CI 0.72 to 1.01 and OR 0.92, 95% CI 0.76 to 1.12, respectively).

Exclusion of the large randomized JUPITER trial did not bring any significance to statin use regarding a decrease in VTE risk (OR 0.93, 95% CI 0.82 to 1.07), they said.

The JUPITER trial comprised nearly 18,000 healthy men and women taking either rosuvastatin 20 mg daily or placebo, and found statin use resulted with a significant reduction in cardiovascular events.

Secondary analysis of the trial found some evidence associating statin use with a nearly 40% reduction in VTE (N Engl J Med 2009; 360:1851-1861). However, Rahimi and colleagues noted that the number of events was low and the observed benefit could have been due to chance.

They pointed out that smaller and experimental studies examining the role of statins in VTE have been "somewhat contradictory."

However, because arterial and venous thrombosis share some common risk factors, there were high hopes for statins to have a beneficial effect on VTE, they wrote.

"Stories too good to be true may nevertheless be true, but need to be approached with ample skepticism," wrote Frits Rosendaal, MD, of Leiden University Medical Center in The Netherlands, in an accompanying editorial.

Rosendaal pointed out that statins have been attributed with having beneficial effects that go beyond lipid lowering, including in heart failure, arrhythmia, macular degeneration, fatty liver disease, and about a dozen other conditions.

With so many benefits linked to statins, it's important to determine "noncausal explanations," he said.

In the current study, the 22 trials comparing statin use with no statin use comprised 105,759 participants, while the seven trials comparing intensive versus standard dose statin therapy comprised 40,594 participants.

Studies in both groups collected information on venous thromboembolic events but did not necessarily publish it.

In seven trials that included patients without prior cardiovascular disease, the use of statins resulted in a significant 38% reduction in the risk of VTE. However, when researchers excluded the JUPITER trial, the significance did not remain.

Researchers also did not find any benefits when they controlled for statin type.

"Overall, the results from this meta-analysis do not support the suggestion that statins (or higher doses of statins) reduce the risk of venous thromboembolic events substantially, although a more moderate reduction in risk up to about one-fifth cannot be ruled out," they concluded.

Both the study authors and the editorialist praised the study for certain strengths including the fact that results are based on randomized studies and the large numbers of patient years.

However, Rosendaal noted there could be bias due to outcome misclassification, as many trials regarded VTE as an afterthought.

Rahimi and colleagues said the study was potentially limited by including unpublished data.

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